PROJECT SUMMARY: CORE B The overall theme of this PPG is to further understand the molecular mechanisms of von Willebrand Disease (VWD). Each Project will study unique quantitative and qualitative aspects of von Willebrand factor (VWF) and VWD which will involve many next-generation sequencing (NGS) experiments. Since the sequence data will require extensive computational, bioinformatic and statistical analyses, we have established a Genomics and Bioinformatics Core to serve these critical needs. In addition, this Core will provide a major data-storage and data-sharing function for both this PPG and for investigators worldwide. This Core will have three Specific Aims. Aim 1 will focus on performing all the NGS and analysis for this PPG. The Core personnel will work closely with Project investigators in the design of proposed experiments, and will provide standard analysis of both coding and noncoding sequences for each project. Core B will produce extensive upstream analyses of VWF, RNA seq, genetic and epigenetic genome wide sequences and thorough genomic analyses of patients with low VWF levels but no mutations in VWF. Critical to this application, the Core personnel will also provide data interpretation and additional follow-up data-driven iterative analyses as are often required. This will permit major increase in efficiency by having computational biologists dedicated to this PPG; will offer an iterative approach since analysis of NGS data is complex and experiment driven and will provide consistency regarding analytic approaches. Aim 2 will guarantee data storage, management and transfer. The Genomics and Bioinformatics Core will utilize a newly generated genomic Analytic Platform, which will be exclusive to this application. This platform will be the input conduit and repository for all raw sequencing data and for all NGS analyses in this PPG. All relevant genomic results will be transferred to the Velos clinical database in Core A, where they will be incorporated with phenotype/outcome data to generate a user-friendly interface that enables the simultaneous queries by PPG investigators of phenotype and VWF sequence variants, as well as other genes involved in VWD. Aim 3 will be focused on providing local and public data sharing. We will ensure that raw and analyzed sequencing data are submitted to stable repositories that are accepted by the research community and in accordance with NIH Data Sharing policy. Therefore, a major goal of the Genomics and Bioinformatics Core will be to expand public access to the generated genomic data by interactive public web tools. Within the last year of the PPG we will generate a public web site with a user-friendly interface that enables queries on multiple VWF sequence variants, other genes involved in VWD, and phenotype datasets simultaneously. Ultimately Core B represents a central conduit for genomic and bioinformatics flow of data of this PPG therefore contributing significantly to further understanding the genetics basis of VWD.